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F.D.A. Approves Genetic Drug to Treat Rare Disease

The Food and Drug Administration approved a new drug Tuesday that not only treats a rare inherited disorder that causes extremely high cholesterol levels and heart attacks by age 30, but does so using a long-sought technology that can shut off specific genes that cause disease.

The drug, Kynamro, which was invented by Isis Pharmaceuticals and will be marketed by Sanofi’s Genzyme division, is unlikely to be a blockbuster. It has some worrisome side effects and there might be no more than a few hundred people in the United States with the disease, known as homozygousfamilial hypercholesterolemia, or HoFH.

Still, Kynamro could become the first commercial success for the gene silencing technique, which is known as antisense, and which some experts say is finally poised to fulfill its promise after over two decades of research and numerous disappointments.

“What many people have been waiting for is validation where someone actually makes a profit and where patients actually benefit,” said Arthur M. Krieg, chief executive of RaNA Therapeutics, an antisense drug developer in Cambridge, Mass.

Isis, which is based in Carlsbad, Calif., has been pursuing antisense technology since the company’s founding in 1989, spending about $2 billion. It had one drug approved in 1998 for an infection associated with AIDS, but the drug did not sell well and some experts said it did not really use the gene-silencing mechanism.

Isis’s experience contrasts with that of Gilead Sciences, which was also founded in the late 1980s to pursue antisense technology. It gave up after several years — selling the patents it no longer needed to Isis — and went on to develop antiviral drugs using other techniques. It is now a biotech superstar with a market value of $59.8 billion, compared with $1.4 billion for Isis.

Stanley T. Crooke, the founder and chief executive of Isis since its inception, said the long period of development was not unusual for a new technology.

“I told people it would be at least 20 years and $2 billion before we knew if the technology would work,” he said in an interview Tuesday. “We think it’s a seminal day for the technology and the company.”

Isis or its partners are developing drugs to lower triglycerides, treat spinal muscular atrophy and reduce scarring from operations, among other things. The partners include Biogen Idec, Pfizer and AstraZeneca.

Two rival antisense companies, Sarepta Therapeutics and Prosensa are developing drugs for muscular dystrophy that have shown promise in early clinical trials.

Still, Dr. Cy Stein, a longtime antisense researcher, said it was too early to say that antisense had arrived. There have been false dawns in the field before.

Antisense drugs work essentially by shooting the messenger. The recipe to make a protein is carried from a gene in the nucleus into the body of a cell by a single strand of RNA, called messenger RNA.

Antisense drugs are small snippets of synthetic DNA or RNA that bind to that messenger RNA in a way that inactivates or destroys it.

In theory, an antisense drug can be made to shut down any gene, providing a means to develop a virtually unlimited number of drugs. But in practice, it has been difficult to deliver the drugs into cells with sufficient potency and lack of toxicity. Companies have developed ways to chemically modify the drugs to help in that regard.

Kynamro, known generically as mipomersen, inhibits action of a gene, apolipoprotein B, that is involved in the formation of particles that carry cholesterol in the blood.

If untreated, people with HoFH can have levels of LDL cholesterol, the so-called bad cholesterol, as high as 1,000 milligrams per deciliter. A level of 130 or less for LDL is generally considered desirable.

Statins work for these patients and have helped increase the typical life span to 33 years, from 18, but further cholesterol reduction is needed. Patients can also have their blood cleansed of cholesterol by being connected to a machine for a few hours once a week.

Patients in the main clinical trial of Kynamro started with LDL levels of around 400. After 26 weeks of treatment, those getting Kynamro had a mean decline in LDL cholesterol of 24.7 percent compared with a decline of 3.3 percent for those getting a placebo.

The label for Kynamro will carry a boxed warning about potential liver damage. Other side effects include injection-site reactions and flulike symptoms.

Kynamro will share the market with Juxtapid, a drug developed by Aegerion Pharmaceuticals that won approval last month.

In October, an F.D.A. advisory committee voted 13-to-2 in favor of approval of Juxtapid but only 9-to-6 in favor of Kynamro, largely because of concern about side effects. Juxtapid is a once-a-day pill, while Kynamro is injected once a week.

Genzyme has not announced the price for Kynamro but it might be similar to that of Juxtapid, which costs $235,000 to $295,000 a year, similar to some other drugs for extremely rare conditions.

A version of this article appears in print on January 30, 2013, on page B3 of the New York edition with the headline: Approval for Genetic Drug To Treat a Rare Disease. Order Reprints|Today's Paper|Subscribe